Sustained hyperosmolarity increses TGF-beta1 and Egr-1 expression in the rat renal medulla.

BACKGROUND: Although TGF-ss and the transcription factor Egr-1 play an important role in both kidney fibrosis and in response to acute changes of renal medullary osmolarity, their role under sustained hypo- or hyperosmolar conditions has not been elucidated. We investigated the effects of chronic hypertonicity and hypotonicity on the renal medullary TGF-ss and Egr-1 expression. METHODS: Male adult Sprague Dawley rats (n = 6/group) were treated with 15 mg/day furosemide, or the rats were water restricted to 15 ml/200 g body weight per day. Control rats had free access to water and rodent chow. Kidneys were harvested after 5 days of treament. In cultured inner medullary collecting duct (IMCD) cells, osmolarity was increased from 330 mOsm to 900 mOsm over 6 days. Analyses were performed at 330, 600 and 900 mOsm. RESULTS: Urine osmolarity has not changed due to furosemide treatment but increased 2-fold after water restriction (p < 0.05). Gene expression of TGF-ss and Egr-1 increased by 1.9-fold and 7-fold in the hypertonic medulla, respectively (p < 0.05), accompanied by 6-fold and 2-fold increased c-Fos and TIMP-1 expression, respectively (p < 0.05) and positive immunostaining for TGF-ss and Egr-1 (p < 0.05). Similarly, hyperosmolarity led to overexpression of TGF-ss and Egr-1 mRNA in IMCD cells (2.5-fold and 3.5-fold increase from 330 to 900 mOsm, respectively (p < 0.05)) accompanied by significant c-Fos and c-Jun overexpressions (p < 0.01), and increased Col3a1 and Col4a1 mRNA expression. CONCLUSION: We conclude that both TGF-ss and Egr-1 are upregulated by sustained hyperosmolarity in the rat renal medulla, and it favors the expression of extracellular matrix components

Seeking legitimacy through CSR: Institutional Pressures and Corporate Responses of Multinationals in Sri Lanka

Arguably, the corporate social responsibility (CSR) practices of multinational enterprises (MNEs) are influenced by a wide range of both internal and external factors. Perhaps most critical among the exogenous forces operating on MNEs are those exerted by state and other key institutional actors in host countries. Crucially, academic research conducted to date offers little data about how MNEs use their CSR activities to strategically manage their relationship with those actors in order to gain legitimisation advantages in host countries. This paper addresses that gap by exploring interactions between external institutional pressures and firm-level CSR activities, which take the form of community initiatives, to examine how MNEs develop their legitimacy-seeking policies and practices. In focusing on a developing country, Sri Lanka, this paper provides valuable insights into how MNEs instrumentally utilise community initiatives in a country where relationship-building with governmental and other powerful non-governmental actors can be vitally important for the long-term viability of the business. Drawing on neo-institutional theory and CSR literature, this paper examines and contributes to the embryonic but emerging debate about the instrumental and political implications of CSR. The evidence presented and discussed here reveals the extent to which, and the reasons why, MNEs engage in complex legitimacy-seeking relationships with Sri Lankan institutions

An Analysis of Private School Closings

We add to the small literature on private school supply by exploring exits of K-12 private schools. We find that the closure of private schools is not an infrequent event, and use national survey data from the National Center for Education Statistics to study closures of private schools. We assume that the probability of an exit is a function of excess supply of private schools over the demand, as well as the school's characteristics such as age, size, and religious affiliation. Our empirical results generally support the implications of the model. Working Paper 07-0

Four Design Criteria for Any Future Contractarian Theory of Business Ethics

This article assesses the quality of Integrative Social Contracts Theory (ISCT) as a social contract argument. For this purpose, it embarks on a comparative analysis of the use of the social contract model as a theory of political authority and as a theory of social justice. Building on this comparison, it then develops four criteria for any future contractarian theory of business ethics (CBE). To apply the social contract model properly to the domain of business ethics, it should be: (1) self-disciplined, i.e., not aspire results beyond what the contract model can realistically establish; (2) argumentative, i.e., it should seek to provide principles that are demonstrative results of the contractarian method; (3) task-directed, i.e., it should be clear what the social contract thought-experiment is intended to model; and (4) domain-specific, i.e., the contractarian choice situation should be tailored to the defining problems of business ethics

The democratic interface: technology, political organization, and diverging patterns of electoral representation

Democracies are experiencing historic disruptions affecting how people engage with core institutions such as the press, civil society organizations, parties, and elections. These processes of citizen interaction with institutions operate as a democratic interface shaping self-government and the quality of public life. The electoral dimension of the interface is important, as its operation can affect all others. This analysis explores a growing left-right imbalance in the electoral connection between citizens, parties, elections, and government. This imbalance is due, in part, to divergent left-right preferences for political engagement, organization, and communication. Support on the right for clearer social rules and simpler moral, racial and nationalist agendas are compatible with hierarchical, leader-centered party organizations that compete more effectively in elections. Parties on the left currently face greater challenges engaging citizens due to the popular meta-ideology of diversity and inclusiveness and demands for direct or deliberative democracy. What we term connective parties are developing technologies to perform core organizational functions, and some have achieved electoral success. However, when connective parties on the left try to develop shared authority processes, online and offline, they face significant challenges competing with more conventionally organized parties on the right

Large-Scale Evidence for the Effect of the COLIA1 Sp1 Polymorphism on Osteoporosis Outcomes: The GENOMOS Study.

Background Osteoporosis and fracture risk are considered to be under genetic control. Extensive work is being performed to identify the exact genetic variants that determine this risk. Previous work has suggested that a G/T polymorphism affecting an Sp1 binding site in the COLIA1 gene is a genetic marker for low bone mineral density (BMD) and osteoporotic fracture, but there have been no very-large-scale studies of COLIA1 alleles in relation to these phenotypes. Methods and Findings Here we evaluated the role of COLIA1 Sp1 alleles as a predictor of BMD and fracture in a multicenter study involving 20,786 individuals from several European countries. At the femoral neck, the average (95% confidence interval [CI]) BMD values were 25 mg/cm2 (CI, 16 to 34 mg/cm2) lower in TT homozygotes than the other genotype groups ( p &lt; 0.001), and a similar difference was observed at the lumbar spine; 21 mg/cm2 (CI, 1 to 42 mg/cm2), ( p = 0.039). These associations were unaltered after adjustment for potential confounding factors. There was no association with fracture overall (odds ratio [OR] = 1.01 [CI, 0.95 to 1.08]) in either unadjusted or adjusted analyses, but there was a non-significant trend for association with vertebral fracture and a nominally significant association with incident vertebral fractures in females (OR = 1.33 [CI, 1.00 to 1.77]) that was independent of BMD, and unaltered in adjusted analyses. Conclusions Allowing for the inevitable heterogeneity between participating teams, this study—which to our knowledge is the largest ever performed in the field of osteoporosis genetics for a single gene—demonstrates that the COLIA1 Sp1 polymorphism is associated with reduced BMD and could predispose to incident vertebral fractures in women, independent of BMD. The associations we observed were modest however, demonstrating the importance of conducting studies that are adequately powered to detect and quantify the effects of common genetic variants on complex diseases

Application of the health assessment questionnaire disability index to various rheumatic diseases

Purpose\ud \ud To investigate whether the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) can serve as a generic instrument for measuring disability across different rheumatic diseases and to propose a scoring method based on item response theory (IRT) modeling to support this goal.\ud \ud Methods\ud \ud The HAQ-DI was administered to a cross-sectional sample of patients with confirmed rheumatoid arthritis (n = 619), osteoarthritis (n = 125), or gout (n = 102). The results were analyzed using the generalized partial credit model as an IRT model.\ud \ud Results\ud \ud It was found that 4 out of 8 item categories of the HAQ-DI displayed substantial differential item functioning (DIF) over the three diseases. Further, it was shown that this DIF could be modeled using an IRT model with disease-specific item parameters, which produces measures that are comparable for the three diseases.\ud \ud Conclusion\ud \ud Although the HAQ-DI partially functioned differently in the three disease groups, the measurement regarding the disability level of the patients can be made comparable using IRT methods\u

An Integrated Framework for Intersectorality: Nonprofitness and Its Influence on Society and Public Administration Programs

Cross-sector interactions have long occurred in the public delivery of goods, services, and interests. While scholars have often addressed cross-sector interactions using the dimensions of publicness (state) and privateness (market), an intersectoral framework necessitates the understanding and incorporation of nonprofitness to account for the dimensions of nonprofits along the public-private continuum. This article proposes a framework for identifying the dimensions of nonprofits in an intersectoral world and draws on relevant examples to illustrate the presence and influence of nonprofitness. The article then focuses on the future of education in the field of public administration and, in light of the proposed framework, makes and considers recommendations to help educational programs better equip students to appreciate work across sectors